Team

The people in the lab

Gioele La Manno

ELIFR Scholar

Outreach

Popular science, News and Media

New method reveals cell development

Researchers at Karolinska Institutet and Harvard Medical School report in the journal Nature that they have developed a technique for capturing dynamic processes in individual cells. Apart from studying disease processes, the method can be used to observe in detail how specialised cells are formed during embryonic development.

Midbrain study gives boost to Parkinson’s research

Two research teams at Karolinska Institutet have identified the dopamine-producing cells in the midbrain of mice and humans. They have also developed a method of assessing the quality of in-vitro cultured dopamine-producing cells, which can be of great benefit to research on Parkinson’s disease. The results are published in the academic journal Cell.

Special nerve cells cause goose bumps and nipple erection

The sympathetic nerve system has long been thought to respond the same regardless of the physical or emotional stimulus triggering it. However, in a new study from Karolinska Institutet published in the journal Nature Neuroscience, scientists show that the system comprises different neurons that regulate specific physiological functions, such as erectile muscle control.

Conversion of brain cells offers hope for Parkinson’s patients

Researchers at Karolinska Institutet have made significant progress in the search for new treatments for Parkinson’s disease. By manipulating the gene expression of non-neuronal cells in the brain, they were able to produce new dopamine neurons. The study, performed on mice and human cells, is published in the prestigious scientific journal Nature Biotechnology.

Latest Posts

Our work on RNA velocity, the time derivative of gene expression, is now out in Nature. A lot of interesting new evidence and analysis added to the initial bioarxiv preprint. We put great attention to feature possibilities and the limits of the estimation approach. velocyto software is mature and ready to use. Enjoy!

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Over the last few days I have been at the École Polytechnique Fédérale de Lausanne (EPFL) Lausane, Switzerland. The reason of this little trip is that EPFL recently opened a special position at their School of Life Sciences….

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Congratulations to Lars and Simone! This week Simone Codelluppi and Lars Borm, in our lab have been releasing to the world their creation: osmFISH, a fantastic technique they have been optimizing to perfection! I really reccomand to read the preprint here

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Single-cell RNA-seq measurements provide a powerful approach for studying complex biological tissues. Some of the more interesting contexts involve dynamic processes, such as development or disease progression. However single-cell measurements only capture a snapshot of a transcriptional state at a single point in time.

Several approaches have been developed to infer dynamic processes, such as branching lineages, from this scRNA-seq. Usually those methods require …

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Selected Publications

Here we show that RNA velocity - the time derivative of RNA abundance - can be estimated by distinguishing unspliced and spliced mRNAs in standard single-cell RNA sequencing protocols. RNA velocity is a vector that predicts the future state of individual cells on a timescale of hours.
Nature, 2018

We used RNA sequencing of half a million single cells to create a detailed census of cell types in the mouse nervous system. We mapped cell types spatially and derived a hierarchical, data-driven taxonomy.
Cell, 2018

We discover: Species differences in developmental timing and cell proliferation. Multiple radial glia subtypes biased toward distinct fates. Adult dopaminergic neuron subtypes emerge postnatally. A machine learning method to score dopaminergic differentiation of stem cells
Cell, 2016

We explored the heterogeneity of mouse stellate and thoracic ganglia and found an unexpected variety of cell types. We identified specialized populations of nipple- and pilo-erector muscle neurons. Our results provide compelling evidence for a highly sophisticated organization of the sympathetic nervous system into discrete outflow channels that project to well-defined target tissues and offer mechanistic insight into how diversity and connectivity are established during development.
Nature Neuroscience, 2016

Publications

. RNA velocity in single cells. Nature, 2018.

PDF Supplementary

. Molecular architecture of the mouse nervous system. Cell, 2018.

PDF Dataset Supplementary

. Spatial organization of the somatosensory cortex revealed by cyclic smFISH. Nature Methods, 2018.

PDF DataPage

. STRT-seq-2i: dual-index 5ʹ single cell and nucleus RNA-seq on an addressable microwell array. Scientific Reports, 2017.

PDF Supplementary

. Molecular analysis of the midbrain dopaminergic niche during neurogenesis. biorxiv, 2017.

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. Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson's disease model. Nature Biotechnology, 2017.

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. Molecular diversity of midbrain development in mouse, human, and stem cells. Cell, 2016.

PDF Supplementary Data visualizations

. Visceral motor neuron diversity delineates a cellular basis for nipple-and pilo-erection muscle control. Nature Neuroscience, 2016.

PDF Supplementary

. Single-cell transcriptomics reveals that differentiation and spatial signatures shape epidermal and hair follicle heterogeneity. Cell Systems, 2016.

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. Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system. Science, 2016.

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. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science, 2015.

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. Quantitative single-cell RNA-seq with unique molecular identifiers. Nature methods, 2014.

PDF Supplementary

Software

Below the scientific software I have been working on:

velocyto

A package for the analysis of expression dynamics in single cell RNA seq data. For more information go to the velocyto homepage

cytograph

A tool for building analysis pipeline for big single cell RNA sequencing projects

loompy

Core implementation the standard format to store and work with single cell expression data. For more information go to the loompy homepage

nbregression

Negative binomial generalized linear model for single cell expression data

cmdstan-py

An alternative, lightweight, python interface to the Bayesian Modeling language Stan.

BackSPIN

Reference implementation of the clustering algorithm described in Zeisel et al. 2015

ceftools

An older file format designed to store smaller single-cell RNA seq datasets